Preparation of 2-cyanopyridines



Patented Jan. 10, 1956 PREPARATION OF 2 CYANOPYRIDINES Ivan Maxwell Robinson and George John Janz, McMasterville, Quebec, Canada, assignors to Canadian Industries Limited, Montreal, Quebee, Canada, a corporation of Canada No Drawing. Application April 19, 1946, Serial No. 663,632. In Canada August 17, 1945 This invention relates to a process for reacting cyanogen with 1,3-dienes. More particularly it relates to a process for the preparation of 2-cyanopyridine and novel derivatives thereof by the reaction of cyanogen with butadiene or substituted 1,3-dienes.

It is an object of the present invention to provide a method for reacting cyanogen with 1,3- dienes. A further object is to prepare Z-cyanopyridine and novel substituted 2-cyanopyridines. Other objects of this invention will be apparent from the description given hereinafter.

The objects of this invention are attained by reacting cyanogen with a diene such as butadiene in either liquid or vapour phase, at atmospheric or superatmospheric pressures and at tempera- 5 Claims. (Cl. 260296) I and dihydropyridine derivatives have not been tures ranging from approximately 90 to 700 C.

The products obtained are Z-cyanopyridines or substituted 2-cyanopyridines.

It has been found that cyanogen may be reacted with 1,3 -dienes of the general formula in which R1 and R4 represent alkyl substituents or hydrogen and R2 and R3 represent alkyl, nitrile or halogen substituents or hydrogen. It seemslikely that the mechanism of this reaction involves a Diels-Alder type of condensation with subsequent elimination of hydrogen. The nitrile groups in this case act as dienophiles according to the usual meaning of the term in reference to Diels-Alder condensations (Norton, Chem. Rev., 31, 1941). A dihydropyridine derivative first forms, through a 1,4 addition of cyanogen to the 1,3-diene, which then dehydrogenates to yield a in'Which'Ri, R2, R3 and R4 have the significance isolated in this reaction. When both nitrile groups take part in the Dials-Alder condensation a dipyridyl derivative results.

The mechanism described above is proposed merely as a possible course which the reaction. may follow. It is not intended that the explanation will in any way limit or influence the scope of the claims. 7

The condensation of 1,3-dienes and cyanogen according to the process of this invention may be conducted at temperatures ranging from about 90 C. to about 700" C. Temperatures beyond the extremes noted may be used, but slower reaction rates result at the lower temperatures, and pyrolysis is severe at higher temperatures. At the lower part of the temperature range, superat-. mospheric pressure is required to obtain reasonable rate of reaction with certain dienes, as for; example, butadiene. At the higher part of the temperature range with certain 1,3-dienes severe pyrolysis of the compounds results in low yields. In the case of butadiene a range of 450-500 C. is preferred at atmospheric pressure.

The reaction, according to the process of this I invention, may be carried out at atmospheric pressure,- or at any'higher value, depending only on the capacity of the equipment to withstand the pressure used.

Contact times suitable for the process of thisinvention may be varied widely. At about 700 C. in the'vapour phase and at atmospheric pressure using butadiene and'cyanogen, contact times of from 0.5 to seconds are suitable as shown in Example II.- At about 500 C. under otherwise similar conditions 18 to seconds are suitable as shown in Example I. The contact time does not necessarily fall Within the above ranges, but may be varied widely. 'The preferred contact time for a particular set of reactants will be influenced by the temperature.

The above-described process may be conducted in the liquid or vapour phase and either by a batch or continuous process.

Thereaction products are condensed from the unreacted material at about 20 C. and the unreacted 1,3-diene and cyanogen are recovered by noted above. The intermediate dihydropyridine 68 condensation at low temperatures, such as that of a dry-i ce acetone trap.

The products of this invention may be isolated by distillation of the crude reaction mixture'preferably under reduced pressure. They may be further purified byrecrystallization from suitable solvents. Other methods of isolation and purification such as, for example, solvent extraction, may be used, as is, of course, apparent to one skilled in the art.

The detailed practice of the invention is illusdrochloride prepared in this manner the free picolinic acid is easily prepared The acid thus isolated melted at 135-136" C. (corrected); the literature values are 136-137 C., 134.5-136 C.

trated by the following examples. There are, of 5 for picolinic acid. By heating the 2-cyanopyrcourse, many forms of the invention other than idine with lime, it is decarboxylated and pyrthese specified embodiments. idine may be separated from the mixture by dis- Example I.1,3-butadiene and cya gen in a tillation. It was identified by its boiling point, molar ratio of 1.0210 are passed through a steel and by the X-ray diffraction pattern of its picvapour phase reactor for a total time of 13 hours rate. The temperature of the reactor is maintained at Investigation of the fraction of the crude prodabout 480 C. and the contact time of the gases uct boiling higher than 2-cyanopyridine has in the reaction zone is about 87 seconds. The shown the presence of 2,2-dipyridy1. It is septotal recovery, as liquid product and. unreacted arated by distillation in the Whitmore-Fenske butadiene and cyanogen, is 84.5% by weight of 15 column at 133-1345 C., 11 mm. HG pressure, the initial material input. The yield of product, and has the following properties: (I) M. P. (imstripped from the gases leaving hot reaction pure) 56.6" C. (II) B. P. 760 mm. Hg 270-272 (3., zone by a water-cooled condensing system is (III) picrate, M. P. 154-155.5 C., (IV) characterabout 3.8% by weight, calculated on the total istic colour reaction with ferrous ions. The propinput of butadiene and cyanogen. After re- 2 erties reported in the literature for 2,2'-dipyridyl moving the more volatile portions, fractional are (I) M. P. 69.5? C., (II) B. P. 760 mm. Hg 272'.5 distillation at 8-12 mm. Hg pressure in a Whit- 0., (III) picrate M. P. 154-l55.5 C., (IV) characmore-Eenske column is used to separate the 2- teristic colour reaction with ferrous ions. cyanopyridine from the crude liquid product. Example II.-1,3-butadiene and cyanogen in a After 47% of the crude product is found to be molar ratio of 0.77:1.0 are passed through a steel 2.-cyanopyridine. vapour phase reactor for a total time of 8 hours. TableI summarizes this data and. lists for com- The reactor temperature is maintained at about parison the results of two other trials at different 680? C. and the, contact time of the gases in the contact times. reaction zone is about 33 seconds. The total. re-

Table I Z-Cyano Temp.,0. 5%;? ,i it n iii ii fi H e v e g i r i i c lfit 1 32; ifigfii Pyi i i i iiwpa Duration (approx) Secs Cyanogen, cent of Input, cent of Input, Crude Prod cent of Input, of Run moles by welght) by Weight) by weight)" by weight) Hours 480. 98 l.0:1.0 84.5 38.5 41 18.1 is 480 120 0. 85:1.0 74. 2s. 5 4s 13. 7 o. s 470-490 25 1.28:1.0 85.5 18.7 33 6.17 1.66

e z-Q py d e s para ed L hQ crud? covery, as liquid product, unreacted butadiene product by fractional distillation, mentioned and cyanogen is 53.7% by weight of the initial above, is further purified y filtering; 0fi=- the material input. The yield of product, stripped crystals at 0? (2., and by washing and recrysfrom the gases leavin the hot reaction tube bytallizing them from cold ether. It is found. to 45 a water cooled condensing system is about 36.6% have the following properties: (I) melting point, by weight of the total input of butadiene and 27-.0- 2 7.5 C. uncorrected; literature, 29? C 26 cyanogen. After removing the more volatile por- C.; (II) refractive index 711 1.5212, density tions, fractional distillation in a Wh-itmore- 2 =1 0810; (III), boiling, point, 22 2 -227? Qpn- Fenske column at 8-12 mm. Hg pressure is used corrected, literature (11) 212 215 0., (b) 222.5: so to separate e 2- p e -t ru 2235. 0.5 (IV) analysis c. 70.00% 4,07%, liquid product. About 33% of the crudeproduct N. 26.04%; theoretical f cunuogc. 69.22%, H. is found to be z-oya opyridine. 337%,}1, 2 691%, Table II summarizes this data and listsfor-- In order to identify the product, picolinic acidcomparison the results of other trials at differ hydrochloride has'been prep ared byfsubjecti ng ent contact times. With the exception of thethe Z-cyanopyridine to hydrolysis withaqueous example at 0.39 second contact time, for which sodium hydroxide, and separating the, acid as they a silica reactor tube was used, all trials were hydrochloride. The results of thefanalysis for carried out inaste l r or.

Table II e p-R0. gg-g i33te?= i rfiittfii i it iiotdtfi 3592 1 6503 tiii toit t Duration (mm ere a ar has; m

Huun $38 3% tiiziz. 3%" it it 2:1 3.75 700. 18 1. 18:1. 0 45 21 23 6.3 1. 5 700 u. 39 11151.0 77.6 13-14 41.5 5.6 a

21.95; theoretical for con6no2ci, -o .45.15, 3,339,.

N. 8.78, 0122.23. Fromthepicolinic acid hy Example II I .-l,3-butadien e. and cyanogen in a molar ratio of 0.95 1.0 are sealed in a high pressuresteel bomb which isthen heated in-a furnace to. the. desired temperature, Table III below is.

".9, record of the pressuredeveloped as-the tern- .perature is increased:

Table III The maximum temperature, 270 C., is above the critical temperature of butadiene and of cyanogen. The liquid product is separated from the solid products of the reaction by extraction with ether, and is obtained in approximately a 30% yield by weight, calculated on the input of cyanogen and butadiene. Fractional distillation of this crude product at 14-15 mm. Hg pressure is used to separate the Z-cyanopyridine which comprises approximately 26% by weight of the crude product.

Example 1V.-1,3-butadiene and cyanogen in a molar ratio of about 0.88:1.0 are sealed in a'glass bomb tube and heated for 28.5 hours at approximately 110 C. From this reaction mixture a liquid product is obtained in a 28-29% yield, calculated on the input of butadiene and cyanogen. Using a Vigreux column for the fractional distillation at -12 mm. Hg pressure of this liquid product, the 2-cyanopyridine is separated from the crude product in about 50-55% yield, by weight (calculated on the crude product).

Example V.Isoprene (2-methylbutadiene-1,3) and cyanogen in a molar ratio of about 0.06:1.0 are passed through a steel vapour phase reactor for a period of 2.5 hours. The temperature of the reactor is maintained at about 500 C. and the contact time of the gases in the hot reaction zone is approximately 86 seconds. The total recovery, as product and unreacted isoprene and cyanogen, is about 62% by weight of the initial material input. The crude liquid product removed from the hot gases leaving the reaction zone by a water cooled condensing system is fractionally distilled in a Vigreux column under reduced pressure. The 2-cyan0picolines are collected in the fraction boiling at 88.5 C., 2 mm. Hg pressure. The yield is about 18% by weight, calculated on the initial input of isoprene and cyanogen.

The mixture of 2-cyanopicolines is purified by several recrystallizations from low boiling ligroin. The mixture, melting at 48-77 C., was found to have the following analysis: 1

which checks for the compound CvHsNz as shown. By heating the mixture with lime, it is decarboxylated and an oil, B. P. 143-148 C. (atmospheric pressure) is obtained. It is reported in the literature that a mixture of beta and gammapicolines boils at 142-146 C. at atmospheric pressure. The presence of gamma-picoline in this decarboxylated mixture has been further confirmed by the preparation of an oxalate and a picrate derivative. The oxalate derivative melted at 137.5-139 C., the published values for gamma-picoline oxalate are 137-138 C., and 139-140 C. The results of the identification of gamma-picoline picrate are: (I) melting point, obs. 161-162" 0., literature 163-164 C.; (II) analysis obs. C. 44.34%, H. 2.77%, N. 17.1%, cal- 6 6111915611 f01C12H1oN407, C. 44.73%, H. 3.13%, N. 17.4%; (III) the X-ray difiraction pattern was identical with that prepared. from authentic gamma-picoline.

Example VI .Chloroprene (z-chlorobutadiene- 1,3) and cyanogen in a molar ratio of about 10210 are passed through a steel vapour phase reactor for a total time of 9.75 hrs. The temperature of the reactor is maintained at approxi-. mately 475 C.-495 C., and the contact time of the gases in the hot reaction zone is about seconds. The total recovery as crude product, unreacted chloroprene and cyanogen, is about 63.1% by weight of the initial material input. The solid material, that has separated from the liquid crude by condensing on the cold glass surfaces, is purified by recrystallization from low boiling ligroin and ether. Its melting point is 83-84 C. The crude liquid product, on fractional distillation in a Vigreux column yields another solid product, that distils over at 108-120 C. at 3-4 mm. Hg. pressure. Its melting point, after recrystallization from low boiling ligroin is 107.5- 108 C. These compounds are isomeric 2-cyanochloropyridines, and are obtained in yields of 3-5% by weight of the initial material input. The analysis found is as follows:

The compound, M. P. 83-84 0., is further identilled as the 2-cyano-5-chloropyridine since hydrolysis yields 5-chloropicolinic acid. (Melting point, with decomposition, found 172-174 C., literature, 169-170, 170 C.) The higher melting isomer is the 2-cyano-4-chloropyridine.

Erample VII.Cyanogen and z-methylpentadime-1,3 in the molar ratio of about 1.16:1.0 are passed through a steel vapour phase reactor for a total time of 4 hrs., 53 minutes. The temperature of the reactor is maintained at approximately 507 0., and the contact time of the gases in the hot reaction zone is about 121 seconds. The total recovery as crude product, unreacted 2- methylpentadiene and cyanogen, is about 75%. The product stripped from the hot gases leaving the reaction zone is obtained in a 61-62% yield, by weight, of the material input and is nearly all solid at room temperature. The solid product is separated from the crude by filtration and is further purified by recrystallization from low boiling ligroin, with the use of decolorizing carbon. It crystalizes in fine white silky needles, of melting point 53-53.5 C. The analyses found are:

Percent 0 Percent N Observed 72. 99, 72. 94 20. 9, 20. 7 Theoretical for C|H3N2 72.7 21. 2

dine thus obtained forms aipicratarecrystallized from ethanol, M 11?. observed 179-180" 0., literature value, 179 C. The :product from the reac-v tion of cyanogen and Z-methylpentadiene therefore iis 2-cyano-4,6-lutidine.

In addition to the -1,3-dienes already mentioned in the examples, the following, for exarripie, are suitable: butadiene; 'z-methyl butadiene; 2,3-di methyl bu'tadiene, 1,3-pentadiene; z-tcyanobuta-z diene; 2-ch1orobutadiene; '2,3 -d'i-chlorobutadiene; 3,4-dimethyl 'heXadiene-ZA; Z-methyl-penta dime-1,3; 2-chloropentadiene 13; fl-cya-nopentadiene-1,3; hexadiene-ZA; fi-methylhexadiene- 1,3; 12,6-dimethyl-octadiene 3,5; hexadiene-LS; 2-cyanohexadiene-1,3; 3-c'ya'nohexadiene-L3; 3- cya'nopentadiene-lfig 3-chloropentaiiiene-2l,'3'; 3- cyanohexadiene-'2,4; 4-cyanohexadiene-2,4; 2- chlomhexanedie-LB; 3-ch1orohexadiene-L3; 3- ohlorohexa'diene-2A; 4-cholorohexadiene-2A; 2- methylhexadiene-l,3; 3-methylhexadiene-i15; 2,3-dimethy1heXadiene-1,3; 3-methylhexadiene- 2,4; 4-methylhexadiene-2A; 3,4-dimethy1hexa- (hone-2,4; l-methylhexadiene-l-,3; 2-methylhexadiene-2,4; 4-methylheXa'diene-l ,3; 5-methylheXa'diene-ZA; '2,fi-dimethylhexadiene-l; "1,4- dimethylheXadiene-L'S'; octadiene-'3,'5.

The above description and examples are intended to be illustrative only. Any modification of or variation therefrom which conforms to the spirit of the invention is intended to beincluded with the scope of the claims.

Having thus described our invention 'what We claim is:

1. A process which comprises passing a gaseous mixture of butadiene and cyanogen in a molar ratio of substantially 1:1 through a reaction chamber maintained at approximately 500 C. at such'a rate that the gas ispresentin the reaction chamber for a period of from between'20 and 120 seconds and cooling the gas emerging from the reaction chamber to condense 2-cyanopyridine.

2. A process Whichcompr'ises passing a gase'ous mixture of isoprene and cyanogen in -':a molar ratio of substantially 1:1 through a reaction chamber maintainedat approximately 500 C. at such a rate that the gas is present in the-reaction chamber for about 100 seconds and cooling the gasemerging from-the reaction chamber to-condense a mixture of 2-cyano-4-picciline and 2- cyano-5-picoline.

3. A process which comprises-passing a gaseous mixture of 2-chlorob1rta diene-1, 3 and'cyanogen ina molar ratio of substantially 111 through 'a reactionchamber maintained at a temperature of approximately 500 (Lat such a rate that the gas is present in the reaction chamber for about 100 seconds and cooling the gas 'emerging from thereaction chamber tocondense a'mixture of 2-cyano-4-chloropyridine and 2-cyano-5 chloropyridine.

8,, 43A process which comprises reacting at a temperature from about to 700 C. :a "gaseous mixture of cyanogen with a 1, 3-diene of the general formula cH=c-c=oH l R2 3 4 wherein R1 and R4 each represent a member of the group consisting of hydrogen and alkyl radicals containing not more than 2 carbon atoms and R2 and R3 each represent a member of the group consisting of hydrogen, chlorine and the methyl radical, and separating the reaction productof the general formula wherein R1, R2, R3 and R4 have the same significance as above defined. v I 5. A process which comprises passing through a reaction chamber maintained at a temperature from about 400 to 700 C. a gaseous mixture of cyanogen and a 1, 3-diene of the general formula I'M 3 4 wherein R1 and R4 each represent a member of the group consisting of hydrogen and alkyl radi .cals containing not more than 2 carbon atoms and R2 and R3 each represent a member of the group consisting of hydrogen, chlorine and the methyl radical, said reactants being present in a ratio of substantially 1:1 and being passed through the reaction chamber at such a rate'that the gaseous mixture is present in the reaction chamber for a period between and 0.3 secends and cooling the gas emerging from the reaction chamber to separate the reaction product of the general formula wherein R1, R2, R3 and R4 have the same sig nificance as above defined. IVAN MAIWIELL ROBINSON. GEORGE JOHNJANZ.

REFERENCES CITED "The following references are of record in the file of this patent:

.Maier Das pyridine und seine Derivatives}? page 206 (1934). 

4. A PROCESS WHICH COMPRISES REACTING AT A TEMPERATURE FROM ABOUT 90* TO 700*C. A GASEOUS MIXTURE OF CYANOGEN WITH A1,3-DIENE OF THE GENERAL FORMULA 